PMID- 30522087
OWN - NLM
STAT- MEDLINE
DCOM- 20190207
LR  - 20190215
IS  - 1768-3254 (Electronic)
IS  - 0223-5234 (Linking)
VI  - 162
DP  - 2019 Jan 15
TI  - (Pyrrolo-pyridin-5-yl)benzamides: BBB permeable monoamine oxidase B inhibitors 
      with neuroprotective effect on cortical neurons.
PG  - 793-809
LID - S0223-5234(18)30963-2 [pii]
LID - 10.1016/j.ejmech.2018.11.009 [doi]
AB  - An extensive study was performed to develop a series of 
      (pyrrolo-pyridin-5-yl)benzamides as reversible MAO-B inhibitors. Compounds 14 
      (NTZ-2020, hMAO-B IC(50) = 1.11 nM, K(i) = 0.56 nM, >9000-fold selective versus 
      MAO-A) and 15 (NTZ-2027, hMAO-B IC(50) = 3.27 nM, K(i) = 1.45 nM, SI > 3058) are 
      identified as the most promising BBB permeable derivatives within the series of 
      (1H-pyrrolo[3,2-b]pyridine-5-yl)benzamides, combining both high potency and 
      selectivity with optimal physicochemical and drug-like properties required for 
      CNS active drugs. Extended photophysical analysis, including single X-ray 
      analysis, quantum-chemical calculations and spectroscopic experiments provided 
      insights into their tautomerism and structural behavioral, which relates to their 
      biologically active form. The reversible MAO-B inhibitor 14 (NTZ-2020) exhibits a 
      neuroprotective effect on cortical neuron survival and induces neurite network 
      outgrowth. These effects are associated with a good BBB penetration of 14 that 
      was confirmed in a triple cell neurovascular unit (NVU) model.
CI  - Copyright (c) 2018 Elsevier Masson SAS. All rights reserved.
FAU - Tzvetkov, Nikolay T
AU  - Tzvetkov NT
AD  - NTZ Lab Ltd., Krasno selo 198, Sofia, 1618, Bulgaria. Electronic address: 
      ntzvetkov@ntzlab.com.
FAU - Stammler, Hans-Georg
AU  - Stammler HG
AD  - Department of Chemistry, University of Bielefeld, Universitatsstr. 25, 33615, 
      Bielefeld, Germany.
FAU - Hristova, Silvia
AU  - Hristova S
AD  - Bulgarian Academy of Sciences, Institute of Organic Chemistry, Centre of 
      Phytochemistry, Acad. G. Bonchev Str., Bl. 9, Sofia, 1113, Bulgaria.
FAU - Atanasov, Atanas G
AU  - Atanasov AG
AD  - Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, 
      05-552, Jastrzebiec, Poland; Department of Pharmacognosy, University of Vienna, 
      Althansstrasse 14, A-1090, Vienna, Austria.
FAU - Antonov, Liudmil
AU  - Antonov L
AD  - Bulgarian Academy of Sciences, Institute of Organic Chemistry, Centre of 
      Phytochemistry, Acad. G. Bonchev Str., Bl. 9, Sofia, 1113, Bulgaria.
LA  - eng
PT  - Journal Article
DEP - 20181113
PL  - France
TA  - Eur J Med Chem
JT  - European journal of medicinal chemistry
JID - 0420510
RN  - 0 (Benzamides)
RN  - 0 (Monoamine Oxidase Inhibitors)
RN  - 0 (Neuroprotective Agents)
RN  - EC 1.4.3.4 (Monoamine Oxidase)
SB  - IM
MH  - Benzamides/*pharmacology
MH  - Blood-Brain Barrier/*metabolism
MH  - Cerebral Cortex/cytology
MH  - Models, Neurological
MH  - Molecular Structure
MH  - Monoamine Oxidase/*drug effects
MH  - Monoamine Oxidase Inhibitors/*metabolism/pharmacology
MH  - Neurons/*drug effects
MH  - Neuroprotective Agents/metabolism/pharmacology
MH  - Permeability
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - ADME
OT  - Benzamides
OT  - MAO inhibitors
OT  - Neuroprotection
OT  - Parkinson's disease
OT  - Synthesis
EDAT- 2018/12/07 06:00
MHDA- 2019/02/08 06:00
CRDT- 2018/12/07 06:00
PHST- 2018/09/23 00:00 [received]
PHST- 2018/11/02 00:00 [revised]
PHST- 2018/11/05 00:00 [accepted]
PHST- 2018/12/07 06:00 [pubmed]
PHST- 2019/02/08 06:00 [medline]
PHST- 2018/12/07 06:00 [entrez]
AID - S0223-5234(18)30963-2 [pii]
AID - 10.1016/j.ejmech.2018.11.009 [doi]
PST - ppublish
SO  - Eur J Med Chem. 2019 Jan 15;162:793-809. doi: 10.1016/j.ejmech.2018.11.009. Epub 
      2018 Nov 13.